Immunology and the cellular response to infection Flashcards

(52 cards)

1
Q

Why do we need an immune system?

A

Attack from outside:

Defence against pathogens (invaders)
Bacteria – meningitis
Viruses – HIV, flu, measles, chicken pox, cov19
Fungi – yeast
Protists – malaria, amoeba
Attack from inside:

Defence against self
Cancer – abnormal body cells

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2
Q

Points of immune entry? Routes of attack?

A

Points of entry:

Respiratory system
Digestive system
Urogenital tract
Break in skin
Routes of attack:

Circulatory system
Lymph system

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3
Q

What is SCID?

A

SCID – extreme immunodeficiency leads to recurrent (fatal) infections

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4
Q

Why not live in a sterile environment?

A

Mice bred in sterile conditions have impaired immune development
Hygiene hypothesis
c-section vs natural birth
Microbiome development can protect against future infection

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5
Q

What 3 stages make up immune response?

A

Immune response:

1st line barriers: skin, acid, bile, mucus

2nd line defence: innate immune response

3rd specialist response: adaptive immune response

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6
Q

What is 1st line response?

A

1st line –nonspecific external defence

Barriers – skin

Traps – mucous membranes, ear wax, cilia

Elimination – coughing, sneezing, urination

Unfavourable environment – stomach acid, sweat, saliva, urine

Lysozyme enzymes – tears, sweat, dissolve bacterial cell walls

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7
Q

What is 2nd line response?

A

2nd line – nonspecific inflammatory response

Damaged cells release a chemical called histamine (makes blood vessels leaky)
Phagocytic white blood cells (WBCs arrive at the site of damage)
WBC eat antigens and present part of the antigen on their surface

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8
Q

What is innate immunity?

A

Present before exposure to any pathogens
Active from birth
Non-specific response to pathogens
Present in all animals and plants (barriers, cellular/chemical defences)

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9
Q

What is 3rd line response?

A

Antibody generation
Specific proteins against individual targets
y-shaped proteins

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10
Q

What is adaptive immunity?

A

Develops after exposure to agents such as microbes, toxins or other foreign substances Highly specific response to each individual pathogen

Present in vertebrates only

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11
Q

What is 3rd line defence?

A

3rd line of defence – antibodies and lymphocytes

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12
Q

What are primary lymphoid organs and the 2 main sites?

A

Development and maturation of immune cells

2 main sites:

Bone marrow

Production of HSCs
Differentiation of HSCs to immune cells
Thymus

T-lymphocyte maturation and selection

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13
Q

What are the secondary lymphoid organs, what do they do?

A

Secondary lymphoid organs

Spleen
Lymph nodes
Mucosal
Mucosal associated lymphoid tissue (MALT)
Generation and organisation of immune response

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14
Q

What counts as foreign material in the body?

A

Pathogens

Bacteria
Virsuses
Fungi
Parasites
Toxins, foreign bodies, donor organs, artificial joints, medical devices

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15
Q

What are the 3 self vs non self theories?

A

Self vs nonself (Burnett 1965)
Infectious non-self theory (Janeway 1989)
The danger model (Matzinger 2002)

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16
Q

What is the self vs non self theory?

A

Self – nonself theory (Burnett 1965)

‘only non-self entities activate the immune system’
So why doesn’t food trigger and immune response?

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17
Q

What is the infectious non-self theory?

A

Infectious non-self theory (Janeway 1989)

‘only entities that express conserved pathogen associated molecular patterns activate the immune system’
So why don’t bacteria in the gut trigger and immune response?

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18
Q

What is the danger model?

A

The danger model (matzinger 2002)

‘the immune response is triggered by danger signals from damaged tissues’

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19
Q

What is the main trigger for an immune response?

A

Immune system is smarter than just seeing something foreign
Certain conserved patterns are recognised on pathogens to identify them as foreign
Danger signals from damaged cells are the main trigger for an immune response
Introduces the concept of tolerance

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20
Q

What is active and passive immunisation?

A

Active immunity occurs naturally when a pathogen infects the body
Passive immunity provides immediate, short term protection
Conferred naturally when antibodies cross from mother to foetus across placenta or in breast milk
Both active and passive immunity can be induced artificially

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21
Q

How can active immunity be induced? How can passive immunity be induced artificially?

A

Active immunity is induced when antigens are introduced into the body via vaccination
Immunisation involves introduction of inactivated, modified, weakened or dead pathogens
Triggers immune response without causing an infection eg MMR vaccine
Passive immunity can be conferred artificially by injecting antibodies into a non-immune individual eg treatment of rabies or ebola

22
Q

How effective is vaccination?

A

Benign form of antigen produces immunological memory
Any encounter with real antigen triggers secondary immune response
Small pox killed over 1 billion people worldwide
Vaccination programs led to eradication of small pox in 1979

23
Q

In what instances is the immune system not a fail safe?

A

Allergy (asthma, hypersensitivity)
Autoimmune diseases (rheumatoid arthritits)
Immune system avoidance (influenza)
Latency (herpes simplex, HIV)
Cancer (HPV)

24
Q

What is innate immunity, what is it comprised of and where is it present?

A

Comprises 1st line and 2nd line defence

Physical and chemical barriers
Cellular defence
Present in all animals and plants

Rapid, non-specific response
Ultimately results in inflammation
Clears damaged cells or infection
Buys time for adaptive immunity to kick in

3 stage response – deflect, detect, destroy

25
What is the reason for inflammation?
Response to tissue damage or microbial invasion - Goals: Bring phagocytes to the injured area Isolate, destroy and inactivate invaders Remove debris Prepare subsequent healing
26
What are neutrophils?
Blood phagocyte Short/half life / high turnover Multilobed nucleus Oxygen related killing – ROS, NADPH oxidase Express TLRs Undergo apoptosis
27
What are macrophages/monocytes?
Resident phagocyte Last for weeks Killing is nitrogen related – RNS, iNOS Express TLR and produce cytokines Eat and clear bacteria and dead cells Monocytes are recruited to tissue differentiate into macrophages
28
What are the 4 stages of phagocytosis?
Attachment Internalisation Degradation Exocytosis
29
What are NK cells?
Lymphocyte-like (no immunological memory) Very aggressive WBCs (5-15% total population) Requires cell-cell contact to functino Kill via release of perforins Pores form in cell membranes Results in cell lysis Target cancerous and virally infected cells
30
What are toll-like receptors and what do they produce?
Recognise specific structures present on pathogens LPS Viral/bacterial genetic material Peptidoglycan Results in signalling cascade and transcription factor activation Production of: Proteins required for cell signalling/activation Interferons Proinflammatory cytokines eg TNF, IL-1
31
How do cells of the immune system know where to go? How do they know what to do when they get there?
Soluble communication factors called cytokines and chemokines
32
What are cytokines?
* Small proteins (<25kDa) * Name means cell movement * Action can be autocrine,paracrine (chemotactic) orendocrine (pyrogenic) * Produced by a wide range of cells – Immune cells e.g.macrophages – Connective tissue e.g. epithelial cells * Can be pro or anti inflammatory
33
What are chemokines?
* Chemotactic cytokines – over 100 intotal * Two large families * Receptors – 7 TMD, G-protein coupled(GPCR). * Most of chemokines interact with multiple receptors, and most of receptors respond to multiple chemokines. * Subset specificity – IL-8 and neutrophils
34
What are interferons? What is their mode of action?
Interferes with viral replication Enhances phagocyte activity of macrophages Stimulates production of antibodies Enhances the killing power of NK cells and cytotoxic T-lymphocytes Slows cell division and tumour growth Mode of action – virus protein synthesis is stopped, virus cannot multiply and dies
35
What are the 3 pathways of activation to the complement system?
3 pathways of activation Classical Alternative Lectin All converge on terminal pathway Results in membrane attack complex (MAC) formation and cell lysis Also produces opsonin and chemoattractant
36
What are humoral defences?
Antibodies Made by B-lymphocytes Detect bacteria and viruses Extracellular – interstitial fluid Ebola/COVID19 survivors – passive immunity
37
What are antigens?
Friend from foe Bacteria, virus, fungus Toxin or diseases cell in body Act as flags to alert adaptive immune system
38
What are b-lymphocytes?
- develop and mature in bone marrow - develops ability to identify friend and foe (immuno-competatance, self tolerance) - 10,000 receptors on surface - each B cell has its own membrane bound receptor - overwhelming odds
39
What are the 6 antibody functions?
1 – neutralisation 2 – opsonisation 3 – agglutination 4 - innate immune cell recruitment 5 – activation of complement system 6 – t-lymphocyte recruitment
40
What is active immunity?
Introduction of dead/modified antigen Secondary response is harder and faster Some disease eg measles are stable Some pathogens mutate eg flu
41
What is passive immunity?
Introduction of antibodies from an immune donor – a temporary stop-gap
42
When is cell-to-cell combat necessary? What is released?
Physical barrier have failed Innate immunity has been overwhelmed Antibodies tried to keep your system healthy Pathogens still managed to invade cells T-lymphocytes are released
43
How do antibodies work?
Cells decorate themselves with parts of the organisms they have destroyed Phagocytes that have engulfed a pathogen display part of the organism on proteins called MHCs on their surface Innate and adaptive cells can do this Professional and amateur antigen presenting cells
44
What do diseased cells have that can make them identifiable?
Diseased cells have modified peptides
45
What are the 3 main immune cells?
Macrophages, dendritic cells and b cells MHC2 present exogenous peptides of pathogens they have engulfed Short amino acid sequences Important – heroes of the adaptive immune system cannot see whole pathogens
46
What are T-lymphocytes?
- made in bone marrow but mature in thymus - 2 main classes – CD4+ helper cells, and CD8+ cytotoxic cells
47
What are helper T-cells? What is a CD4+ helper cell? How do they raise alarms?
Helper T-lymphocytes call the shots CD4+ helper cells Cannot kill pathogens on their own Function as activators of other cells Naive helper T cells have receptors that identify a unique combination of MHC2 and peptide Activated CD4+s clone to helper and memory t-cells They raise the alarm via cytokines - Activates other CD4s – amplify the signal/response Activate CD8s
48
how do CD4s function?
Cytokines from helper cells activate other T-lymphocytes Also finish activation of B-lymphocytes B-cell receptors are randomly generated, can be against self proteins B-cell interacts with protein, engulfs and presents the peptides – then it pauses T helper cells ‘inspects’ the B cell If CD4 binds B cell it releases cytokines and activates B cell leading to antibody production Otherwise B cell goes about its way and does not trigger immune response
49
What are CD8 cytotoxic cells?
Roam body looking for diseased cells Fragments of the very thing killing them displayed in MHC1 Cytotoxic cells can bind to MHC1 and peptide CD8s release enzymes that punch holes in disease cells (perforins, granzymes) Triggers apoptosis killing cell and pathogen inside
50
What are regulatory T cells?
Subset of CD4+ cells Release inhibiting cytokines Prevents adaptive system from producing too many antibodies or cytotoxic cells that can cause damage to self
51
What are autoimmune diseases and 3 examples?
When immune system goes wrong Diabetes – insulin producing cells Rheumatoid arthritis – cartilage and bone Mutiple sclerosis – neural myelin Breakdown of immune regulation
52
How does HIV/AIDs effect cells?
Virus invades CD4 cells – reduces numbers